MPGN

Chronic deposition of debris along the glomerular capillary walls which leads to inflammation.

MPGN is a pattern of injury – diverse aetiology

The deposits can be Ig, complement, fibrin

Glom responds to injury, tries to heal/wall off insult with addtional GBM, creates double contours / tram-trak


Very important to clarify is this is an Ig related disease (more treatable) vs C3G (complement dysregulation, more challenging treatment, worse outcomes)


Histology

Good Review

Light microscopy

  • Two features – inflammation and healing
  • Inflammation is the “proliferative” phase – MPGN – Mesangial and endocapillary hypercellularity
  • Resolving/healing phase – MPGN - mesangial expansion with matrix and thickened capillary walls, cellular interposition with double contour formation

Immunofluorescence

  • Immunoglobulins, Kappa or Lamda light chains, C3

Electron microscopy

  • Mesangial deposits, capillary wall deposits (sub endothelial), cellular interposition and new basement membrane formation – ie. double contours
example 1
example 1

Small White arrows – sub endothelial deposits. Basement membrane is trying to “trap” the deposits as a reaction, just like an abscess being formed and walled off. Incoming cell inflammatory cells (monocytes) get “interposed”

example 2
example 2

More classic appearance here, note entire cell on the left is entrapped, and debris on the right. (images from the Glomcon episode of Sanjeev Sethi, MD, PhD Professor Department of Laboratory Medicine and Pathology Mayo Clinic Rochester, USA Glomcon

MPGN presentation depends on timing along the natural historydapted from Lionaki et al
MPGN presentation depends on timing along the natural historydapted from Lionaki et al

Classification

Immunofluorescence/aetiological classification has replaced the older typing, is often much more informative than as allows more meaningful subdivision

Adapted from Lionaki et al
Adapted from Lionaki et al

~75% are down the left side typically and Ig associated. In the case of Ig positive on IF, then run through a list of differentials similar to this -

Sethi et al
Sethi et al

MPGN “traditional classification” - based on EM, disregarded IF.Not very useful, historical interest mostly. Confusing. Ignore.

Primary:

  • Type 1 sub endothelial
  • Type 2 AKA dense deposit disease - intramembranous
  • Type 3 subendothelial, intramembranous and subepithelial

Secondary:

  • Infection, Hep C was classic

MPGN Treatment

MPGN Outcomes

Best Review

C3G

  • All ages, no sex predilection

  • Nephritic -> nephrotic presentation

  • Typically, present with HTN, proteinuria and haematuria

  • Bright C3, minimal or no Ig - typically 2 orders of magnitude higher than the background Ig staining

  • 2 flavours C3GN, DDD (EM)

  • Usually shows MPGN but other patterns possible e.g. “post infectious”

  • if coexisting IG, more likely to have an autoantibody rather than infection

  • C3GN When associated with infection

  • Some of these have very distant infections which might be associated with complement mutations or residual auto antibodies

G3G Treatment

If associated with Ig/MRUS – clone directed treatment

Haematological remission gives best chance of good renal outcomes and evidence suggests good outcomes

https://pubmed.ncbi.nlm.nih.gov/29759418/

Excluding the monoclonal related disease then IS seems ineffective

https://pubmed.ncbi.nlm.nih.gov/30077216/

C3G Outcomes

50% hit ESKD in 5 years

Usual suspects predict outcome: fibrosis, tubular atrophy, High presenting Cr, proteinuria >3g/24 hours

Misc tips

The renal bx and bone marrow dont match? (e.g. you suspect MPGN from K/L light chains based on marrow but arnt seeing that on the renal bx) - request a paraffin-IF with Pronase digestion and a stain with Heavy-Light chain hybrid antibody to sub-type the IgG - immuno-gold EM to see if the electron dense deposits are composed of a monoclonal light chain.